Development of an effective AIDS vaccine is critical to the ultimate control of the global HIV-1 epidemic. Evaluation of candidate AIDS vaccines in clinical trials is an essential part of this process and is central to the iterative approach required for improving vaccine immunogens and formulations. In this proposal we will state the goals of the Vanderbilt HIV Vaccine Trials Unit (HVTU), define the current state of AIDS vaccine development and critical scientific challenges and describe our plan for implementing and advancing future trials. The Vanderbilt HVTU application will include a consortium between Vanderbilt University and the Cornell University Research Unit in Haiti (GHESKIO) that will have the capacity to perform Phase I clinical trials of candidate AIDS vaccines and advance selected products to Phase II and Phase Ill evaluation. The investigators have extensive experience in the clinical evaluation of vaccines and also bring basic virology and immunology expertise that will contribute to the scientific leadership involved in developing vaccine immunogens, devising vaccine formulations and delivery vehicles, and evaluating immunogenicity, safety, and efficacy in preclinical studies. The investigators are also involved at the national and international level in defining the ethics of performing domestic and international vaccine trials which will be critical during the expansion of studies into developing countries. The focus of the Vanderbilt HVTU consortium will be on the evaluation of novel vaccines vectors (including Venezuelan Equine Encephalitis virus (VEE), adeno-associated virus (AAV), poxvirus, nucleic acid vaccines, and other constructs), the evaluation of cytokine adjuvants (such as IL-12), and combination regimens that incorporate mucosal immunization. Investigators in the Vanderbilt HVTU consortium are engaged at multiple scientific and policy levels of the AIDS vaccine development process, and involved in both domestic and international efforts to pursue the ultimate goal of preventing HIV- l infection and controlling the AIDS epidemic.